The use of long-term opioid therapy for chronic non-cancer pain (CNCP) has increased dramatically in recent years. Although chronic opioid therapy is increasingly common, there are marked differences among patients in treatment outcomes. Providers often increase opioid dose during times of worsening pain, which has the potential to decrease pain intensity, but may increase risk of medication-related adverse effects or opioid misuse. Further, side effects of opioid medications may be dose-dependent. This research will identify clinical factors that predict which patients will have increases in opioid doses. Further, we will examine the benefits and harms of opioid dose escalation and predict which patients are most likely to benefit from this intervention. This multi-site prospective cohort study will includ 600 patients with chronic pain who are currently prescribed opioids. Patients will be evaluated at baseline and every six months for 24 total months. Patients who have an increase in opioid dose (preliminary data indicates 30-35% of the sample) will be evaluated within 1 month of their dose increase and continue with regular six month follow-ups. The Specific Aims of this proposal are to: (1) Evaluate which patient and clinician factors predict opioid dose increases, (2) Determine the differences in trajectories of pain outcomes and adverse effects between patients with and without opioid dose increases, and (3) Assess factors associated with changes in pain intensity and pain-related function over time after controlling for dose changes. We will determine the degree to which patients with opioid dose increases have sustained improvement in pain intensity and function, as well as problems with opioid misuse behaviors and medication-related adverse effects. We also hypothesize that baseline measures of fear avoidance, pain catastrophizing, and self-efficacy will predict which patients benefit from increases in opioid dose. This research has broad implications for clinical care, providing novel data to identify those patients most likely to have increases in their opioid doses, clinician and institutional factors associated with opioid dose increases, the likelihood of positive and negativ outcomes from dose increases (including prescription opioid misuse), and identification of patient factors indicating greatest likelihood of benefit from dose increases. The long-term goal of this research is to improve the treatment of chronic pain by examining the utility of increasing opioid doses in terms of changes in function and potential harms.